Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ischemia markedly depresses fatty acid oxidation and increases fatty acyl-CoA and fatty acylcarnitine levels in the isolated heart during palmitate oxidation. Evidence suggests that the major defect is impaired beta-oxidation due to decreased electron transport rather than to diminished fatty acyl uptake, activation, or intramitochondrial transfer. Important metabolic effects may include decreased mitochondrial adenine nucleotide translocation and altered carnitine-palmity-l-CoA transferase activity.
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PMID:Fatty acid oxidation by ischemic myocardium. 17 11

The distribution of coenzyme A and carnitine between the mitochondrial and cytosolic compartments was determined in rat heart ventricular muscle. The CoA and carnitine levels of homogenate, mitochondrial, and postmitochondrial fractions were determined in nonperfused hearts and in hearts that were perfused under control and ischemic conditions. Using the mitochondrial marker enzymes, citrate synthase and cytochrome c oxidase, the cellular content of mitochondrial protein was determined to be 53 +/- 1.0 (nonperfused), 53.5 +/- 1.5 (control), and 58.1 +/- 2.2 (ischemic) mg/g of wet heart muscle. These values were used to calculate the contribution of the CoA and carnitine located in the mitochondrial compartment to the total cellular levels of CoA and carnitine. Under both control and ischemic conditions, approximately 95% of the cellular CoA was mitochondrial. The percentage of the total cellular carnitine associated with the mitochondria increased from 8 to 9% in nonperfused and control hearts to 25% during ischemia, indicating that a net transfer of carnitine occurred from the cytosol to the mitochondrial matrix.
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PMID:Coenzyme A and carnitine distribution in normal and ischemic hearts. 20 96

A reduction in myocardial oxygen supply during ischemia, not only leads to reduced aerobic ATP production but does not stimulate glycolytic ATP synthesis. The residual aerobically synthesized ATP comes primarily from continued inefficient (i.e., compared to glucose in terms of moles of ATP produced per mole of O2 consumed) oxidation of fatty acids. This leads to elevated tissue levels of long chain fatty acyl-CoA and fatty acyl-carnitine. Both are potentially cell damaging metabolic intermediates. Restriction of glycolysis is due to inhibition of glyceraldehyde-3-phosphate dehydrogenase by accumulated metabolites, such as H+, lactate and NADH. The reduced production of ATP leads to decreased levels of high energy phosphate stores which in turn may impair myocardial mechanical function.
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PMID:Energy metabolism in the ischemic heart. 55 21

The effects of whole heart ischemia on fatty acid metabolism were studied in the isolated, perfused rat heart. A reduction in coronary flow and oxygen consumption resulted in lower rates of palmitate uptake and oxidation to CO2. This decrease in metabolic rate was associated with increased tissue levels of long chain acyl coenzyme A and long chain acylcarnitine. Cellular levels of acetyl-CoA, acetylcarnitine, free CoA, and free carnitine decreased. These changes in CoA and its acyl derivatives indicate that beta oxidation became the limiting step in fatty acid metabolism. The rate of beta oxidation was probably limited by high levels of NADH and FADH2 secondary to a reduced supply of oxygen. Tissue levels of neutral lipids showed a slight increase durning ischemia, but incorporation of [U-14C]palmitate into lipid was not altered significantly. Although both substrates for lipid synthesis were present in higher concentrations during ischemia, compartmentalization of long chain acyl-CoA in the mitochondrial matrix and alpha-glycerol phosphate in the cytosol may have accounted for the relatively low rate of lipid synthesis.
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PMID:Control of fatty acid metabolism in ischemic and hypoxic hearts. 65 17

Inhibition of adenine nucleotide translocase by elevated levels of long chain acyl-CoA esters has been shown to occur during the onset of ischemia in experiments conducted on dogs. Other findings indicate that, as a consequence of translocase inhibition, the production of mitochondrial creatine phosphate was abolished and, in this manner, respiration was slowed to state 4 or an ischemic-like condition. A variety of biochemical, hemodynamic, and ultrastructural evidence further suggest that this inhibition of adenine nucleotide transport in and out of the heart mitochondria may be the initial and key disturbance which "triggers" the more drastic metabolic changes known to occur as the degree of ischemia becomes more severe. The mitochondrial "damage" caused by long chain acyl-CoA ester inhibition of adenine nucleotide translocase appears to be reversible by carnitine.
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PMID:Role of adenine nucleotide translocase in metabolic change caused by ischemia. 120 88

Experiments conducted in healthy mongrel dogs indicate that acyl-CoA levels are raised and adenine nucleotide translocase is inhibited during ischemia. The biochemical findings are accompanied by ultrastructural evidence of myocardial cell damage. These results raise the possibility that the inhibition of adenine nucleotide translocase may be a key disturbance in cellular metabolism.
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PMID:Inhibited adenine nucleotide translocation in mitochondria isolated from ishcemic myocardium. 122 27

Carnitine palmityltransferase activity was measured in mitochondria isolated from control and ischemic dog heart. The ischemic activity demonstrated a decrease in both the Vmax and the Km of the enzyme for 1-carnitine when measured in the presence of 160 muM palmityl-CoA. The kinetic response of the mitochondrial carnitine palmityltransferase to ischemia was mimicked by assay of the enzyme from control mitochondria in a medium of low ionic strength. The effect of ionic strength on enzyme activity was directly correlated with binding of palmityl-CoA to the mitochondrial membranes. The decrease in carnitine palmityltransferase activity in ischemic mitochondria may reflect a decrease in palmityl-CoA binding to the enzyme active site. The depression in ischemic carnitine palmityltransferase activity may represent an early defect in mitochondrial metabolism.
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PMID:Carnitine palmityltransferase activity during myocardial ischemmia and at low ionic strengths. 122 48

L-Propionyl carnitine has been shown to improve the heart's mechanical recovery and other metabolic parameters after ischemia-reperfusion. However, the mechanism of protection is unknown. The two dominating hypotheses are: (i) L-propionyl carnitine can serve as an energy source for heart muscle cells by being enzymatically converted to propionyl-CoA and subsequently utilized in the Krebs cycle (a metabolic hypothesis), and (ii) it can act as an antiradical agent, protecting myocardial cells from oxidative damage (a free radical hypothesis). To test the two possible pathways, we compared the protection afforded to the ischemia-reperfused hearts by L-propionyl carnitine and its optical isomer, D-propionyl carnitine. The latter cannot be enzymatically utilized as an energy source. The Langendorff perfusion technique was used and the hearts were subjected to 40 min of ischemia and 20 min of reperfusion. In analysis of ischemia-reperfused hearts, a strong correlation was found between the recovery of mechanical function and the presence of protein oxidation products (protein carbonyls). Both propionyl carnitines efficiently prevented protein oxidation but L-propionyl carnitine-perfused hearts had two times greater left ventricular developed pressure. The results indicate that both metabolic and antiradical pathway are involved in the protective mechanism of L-propionyl carnitine. To obtain a better insight of the antiradical mechanism of L-propionyl carnitine, we compared the ability of L- and D-propionyl carnitines, L-carnitine, and deferoxamine to interact with: (i) peroxyl radicals, (ii) oxygen radicals, and (iii) iron. We found that none of the carnitine derivatives were able to scavenge peroxyl radicals or superoxide radicals. L- and D-propionyl carnitine and deferoxamine (not L-carnitine) suppressed hydroxyl radical production in the Fenton system, probably by chelating the iron required for the generation of hydroxyl radicals. We suggest that L-propionyl carnitine protects the heart by a dual mechanism: it is an efficient fuel source and an antiradical agent.
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PMID:Antiradical effects in L-propionyl carnitine protection of the heart against ischemia-reperfusion injury: the possible role of iron chelation. 132 84

The purpose of this study was to investigate the energy movement of the normothermic ischemic liver. Liver ischemia was induced in normal and cirrhotic rats, by cross-clamping portal vein and hepatic artery, bypassing the portal blood to the jugular vein through a shunt tube. The levels of ATP of the hepatic tissue was measured before and after hepatic ischemia, by HPLC and 31P-NMR. Before hepatic ischemia, the levels of ATP was greater in normal liver than in cirrhotic liver, but after ischemia it was significantly smaller in normal liver than cirrhotic liver. Generally they say that the greater is the ATP of the tissue, the greater is the viability of the tissue. But this experiment showed the contrary. Cirrhotic liver can't use glucose sufficiently, therefore acetyl-CoA, which is used in TCA-cycle, is derived from the resolution of fatty acid. As a result, free fatty acid and acyl-CoA increase in cirrhotic liver, and suppress Na(+)-K(+)-ATPase. I conclude that the cirrhotic liver can't effectively use ATP to maintain the potential of the liver cells, maybe, because of it's abnormal metabolism of glucose. Therefore, the levels of ATP was greater in cirrhotic liver than in normal liver after hepatic ischemia.
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PMID:[Investigation of hepatic energy metabolism in normothermic hepatic ischemia--comparison between normal and cirrhotic rat liver]. 154 96

During acute myocardial ischemia the metabolism of free fatty acids is impaired. Since the rate of beta-oxidation is reduced, the levels of acil-CoA and long-chain acyl-carnitine increase. The activity of carnitine, which permits the transport of fatty acids into the mitochondria, is reduced both by its transformation in acyl-carnitine and by its release from the cells induced by acute ischemia. The accumulation of fatty acids induces a deterioration of hemodynamic parameters and some impulse formation and conduction disturbances. Since in experimental studies L-carnitine prevents the occurrence of hemodynamic and arrhythmic complications, clinical studies with this compound have been performed during acute ischemia in man. In patients with acute myocardial infarction high doses of L-carnitine induce: a statistically significant increase in urinary concentrations of long- and short-chain carnitine esters; a statistically significant reduction of ventricular arrhythmias during the second day after the onset of symptoms; a reduction of the necrotic area as assessed by electrocardiographic and enzymatic methods.
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PMID:[The role of metabolic therapy in myocardial infarct]. 184 95


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